Targeted proteomic profiling of renal Na(+) transporter and channel abundances in angiotensin II type 1a receptor knockout mice.

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Brooks HL, Allred AJ, Beutler KT, Coffman TM, Knepper MA

Targeted proteomic profiling of renal Na(+) transporter and channel abundances in angiotensin II type 1a receptor knockout mice.

Hypertension. 2002 Feb;39(2 Pt 2):470-3.

PubMed ID

11882592 [ View in PubMed

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Abstract

The renal tubule transporters responsible for Na(+) and water transport along the nephron have been identified and cloned, permitting comprehensive analysis of transporter protein abundance changes in complex physiological models by using a "targeted proteomics" approach. Here, we apply this approach to screen renal homogenates from mice in which the gene for the angiotensin II type 1a (AT(1a)) receptor has been deleted (versus wild-type mice) to determine which sodium transporters and channels are regulated by the AT(1a) receptor at the protein abundance level. In mice maintained on a low NaCl diet (<0.02% NaCl), (1) the abundances of 2 aldosterone-regulated transporters were markedly decreased in knockout versus wild-type mice, namely, the thiazide-sensitive cotransporter and the alpha-subunit of the amiloride-sensitive Na(+) channel (alpha-ENaC); (2) the abundances of beta-ENaC and gamma-ENaC were markedly increased; and (3) there were no significant changes in the abundances of the proximal tubule Na+-H(+) exchanger or the Na(+)-K(+)-2Cl(-) cotransporter of the thick ascending limb. When the experiment was repeated on higher NaCl diets (0.4% or 6% NaCl), the decrease in alpha-ENaC abundance persisted, whereas the other changes were abolished. Analysis of serum aldosterone concentration in AT(1a) knockout mice and wild-type mice on the low NaCl diet revealed the absence of a decrease with AT(1a) gene deletion (11.8 +/- 2.3 nmol/L for knockout mice and 5.7 +/- 0.8 nmol/L for wild-type mice [significantly increased]). These results reveal that the AT(1a) receptor plays an important role in regulation of Na(+) transporter and channel proteins in the "post-macula densa" region of the renal tubule via a mechanism that is not dependent on altered circulating aldosterone concentrations.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Amiloride	Amiloride-sensitive sodium channel subunit beta	Protein	Humans	Yes	Inhibitor	Details